Importance of the B7-2 molecule for low dose melphalan-induced acquisition of tumor-eradicating immunity by mice bearing a large MOPC-315 tumor.
We have previously shown that low dose melphalan (L-phenylalanine mustard; L-PAM) therapy of hitherto immunosuppressed mice bearing a large (20-mm) s.c. MOPC-315 tumor leads to the acquisition of potent CD8+ T cell-mediated antitumor immunity which in turn eradicates the large tumor burden not eradicated by the direct antitumor effects of the drug. Here we show the preferential importance of the B7-2 costimulatory molecule for the curative effectiveness of low dose L-PAM for mice bearing a large MOPC-315 tumor by demonstrating that treatment with anti-B7-2 mAb, but not anti-B7-1 mAb, reduced the percentage of mice cured by the low dose L-PAM. In addition, we show the preferential importance of the B7-2 molecule for the low dose L-PAM-induced acquisition of the ability of tumor-infiltrating lymphocytes from MOPC-315 tumor bearers to secrete IL-2 and IFN-gamma as well as to exert an anti-MOPC-315 CTL effect. The preferential importance of the B7-2 molecule may be due to the higher level of B7-2 than of B7-1 expression on B220+ cells and on tumor cells from the s.c. tumor nodule of low dose L-PAM-treated MOPC-315 tumor bearers and the selective up-regulation of the B7-2 molecule in the draining of these mice. Thus, the B7-2 molecule plays a dominant role in the acquisition of T cell-dependent tumor-eradicating immunity in low dose L-PAM-treated mice bearing a large MOPC-315 tumor, suggesting that one of the mechanisms by which chemotherapy may enhance antitumor immunity is through up-regulation of critical costimulatory molecules that enhance antitumor responses.
Mokyr
M B
MB
Department of Biochemistry, University of Illinois at Chicago 60680, USA.
Kalinichenko
T V
TV
Gorelik
L
L
Bluestone
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D051940:B7-2 Antigen; D004334:Drug Administration Schedule; D005260:Female; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008558:Melphalan / Q000008:administration & dosage* / Q000627:therapeutic use; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010954:Plasmacytoma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D007371:Interferon-gamma; D008558:Melphalan